The long term objectives of this project are to explain a site-specific instability of the 6F1-2 doublet in the Drosophila melanogaster X chromosome, and to determine how a given X chromosome is destabilized by its homologue. The genetic instability in the 6F1-2 doublet will be studied by comparing the DNA of that doublet in stable strain with that of a series of unstable mutants. Restriction mapping, in situ hybridization, cytogenetic analysis, Southern transfer analysis, and genetic studies are some of the methods to be employed. The mutants to be studied were derived from an unstable X chromosome called Uc; they include 33 Uc-induced lethal mutations all having a genetic change in the 6F1-2 doublet, and several revertants of these. Many of the lethal X chromosomes contain structural rearrangements that have been studied cytologically. A highly mobile retrovirus-like transposon, gypsy, has been implicated in the destabilizing action of Uc. Chromosomes which have existed with Uc in the cell acquire many of the properties of Uc, apparently through the transposition of the gypsy element. Also, gypsy transposons have been implicated in the mutation and cryptic transmission of a gene in Drosophila. The genetic impact of gypsy transposons will be analyzed by a combination of genetic and molecular methods, including in situ hybridization and Southern DNA transfer. It is important to understand why Uc is so unstable and to learn how the integrity of a given chromosome or gene is insulted by movable genetic elements. A better understanding of these matters will determine whether they are general phenomena that are expected to occur in all eucaryotic organisms, including humans.